10-62398987-A-G

Position:

• chr10-62398987-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014951.3(ZNF365):​c.962+210A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 152,082 control chromosomes in the GnomAD database, including 33,582 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.66 (33582 hom., cov: 32)
• Consequence: ZNF365 NM_014951.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0290

Genes affected

ZNF365 (HGNC:18194): (zinc finger protein 365) This gene encodes a zinc finger protein that may play a role in the repair of DNA damage and maintenance of genome stability. The N-terminal C2H2 zinc finger motif is required to form a protein complex with PARP1 and MRE11, which are known to be involved in the restart of stalled DNA replication forks. A mutation in this gene may be associated with breast cancer susceptibility. [provided by RefSeq, Mar 2020]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 10-62398987-A-G is Benign according to our data. Variant chr10-62398987-A-G is described in ClinVar as [Benign]. Clinvar id is 1221562.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF365	NM_014951.3	c.962+210A>G		intron_variant		ENST00000395254.8
ZNF365	NM_199450.3	c.924+10411A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF365	ENST00000395254.8	c.962+210A>G		intron_variant		1	NM_014951.3	P1
ZNF365	ENST00000395255.7	c.924+10411A>G		intron_variant		1
ZNF365	ENST00000466727.1	n.325+210A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99739 AN: 151964 Hom.: 33564 Cov.: 32

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.638

Gnomad ASJ AF: 0.656

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.779

Gnomad FIN AF: 0.755

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.647

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.656 AC: 99810 AN: 152082 Hom.: 33582 Cov.: 32 AF XY: 0.662 AC XY: 49236 AN XY: 74360

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.638

Gnomad4 ASJ AF: 0.656

Gnomad4 EAS AF: 0.855

Gnomad4 SAS AF: 0.777

Gnomad4 FIN AF: 0.755

Gnomad4 NFE AF: 0.711

Gnomad4 OTH AF: 0.647

Alfa AF: 0.697 Hom.: 16883

Bravo AF: 0.637

Asia WGS AF: 0.745 AC: 2590 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.3
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2306970; hg19: chr10-64158746;